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K Kojima

Publications and source records attributed to K Kojima.

At least 55 records · Page 3Linked to original sources
PubMed2002

Clinicopathological study of involvement of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor in non-lymphohematopoietic malignant tumors accompanied by leukocytosis.

Involvement of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in non-lymphohematopoietic malignant tumors accompanied by leukocytosis was clinicopathologically investigated. Among 1,778 autopsy cases in the last 20 years, 485 lesions of 439 cases with non-lymphohematopoietic malignant tumors accompanied by leukocytosis with a white blood cell count of 10,000/mm3 or greater during the course were immunohistologically examined for G-CSF and GM-CSF. Three (0.7%) and two cases (0.5%) were G-CSF- and GM-CSF-positive, respectively. GM-CSF mRNA was confirmed by using non-fixed cryopreserved tumor tissues in one case positive for GM-CSF. G-CSF-positive cases were large cell carcinoma of the lung, adenocarcinoma of the colon, and adenocarcinoma of the stomach, and GM-CSF-positive cases were spindle cell carcinoma of the lung and malignant thymoma. In the case with stomach carcinoma, the primary lesion showing moderately differentiated adenocarcinoma was negative, but the lung metastatic lesion showing less differentiated adenocarcinoma was G-CSF-positive. The survival period was six months or less in four out of five positive cases. The highest white blood cell count in five CSF-positive cases was markedly elevated: 29,400-103,500/mm3 (mean: 59,700/mm3). In four cases, excluding one case which may have been markedly affected by chemotherapy, the bone marrow showed hyperplasia, and the number of the granulocyte series cells significantly increased. There were three cases (0.7%) negative for both G-CSF and GM-CSF, although they showed marked leukocytosis (60,000/mm3 or higher) which were higher than the mean count of CSF-positive cases and was not observed in autopsy cases with non-tumorous diseases. Other stimulating factors may be involved in the development of leukocytosis in such cases.

Bone Marrow↗
PubMed2001

High-performance immunoaffinity chromatography, an immunoaffinity membrane for selective removal of plasma components, and safety evaluation of the latter system.

This article reviews our studies on evaluating the suitability of high-performance immunoaffinity chromatography (HPIAC), an immunoaffinity membrane (IAM) for removing unwanted plasma component, and the safety of the IAM. In an attempt to resolve the problem of amyloid deposition in dialysis patients, we used an HPIAC column, bearing anti-beta 2-microglobulin to remove specifically beta 2-MG from human plasma. The use of a membrane as an affinity ligand support was also studied. A specific antibody immobilized on the membrane was highly effective for the removal of rat immunoglobulin E and of a human serum amyloid P component passed through an extracorporeal circulation (EC) system. Biocompatibility of the specific antibody-bearing IAM was also examined. These techniques should prove useful for medical applications and may have broad applicability to the elimination of any unwanted plasma component. The IAM exerts two functions simultaneously, usual dialysis and elimination by immunoaffinity binding. The rat EC model has been applied as an evaluation system for the safety of medical devices in contact with the blood stream. Combining commonly used hemodialysis (HD) membranes with rat EC, we evaluated the elicitation of immunological responses, as well as the effect of repeated EC. The data suggest that this EC model can reproduce similar immunological responses in HD patients, and can be employed to evaluate medical devices and materials for their delayed, systemic, and repeated exposure effects. The EC system described here can reproduce human HD treatment, remove unwanted substances, and evaluate medical devices and materials for toxicological responses.

Animals↗
PubMed2001

Structure and expression of the glycine cleavage system in rat central nervous system.

The glycine cleavage system (GCS) is a mitochondrial multienzyme system consisting of four individual proteins, three specific components (P-, T-, and H-proteins) and one house-keeping enzyme, dihydrolipoamide dehydrogenase. Inherited deficiency of the GCS causes nonketotic hyperglycinemia (NKH), an inborn error of glycine metabolism. NKH is characterized by massive accumulation of glycine in serum and cerebrospinal fluids and severe neuronal dysfunction in neonates. To elucidate the neuropathogenesis of NKH, we cloned cDNAs encoding three specific components of the GCS and studied the gene expression in rat central nervous system. P-, T-, and H-protein cDNAs encoded 1024, 403, and 170 amino acids, respectively. In situ hybridization analysis revealed that P-protein mRNA was expressed mainly in glial-like cells, including Bergmann glias in the cerebellum, while T- and H-protein mRNAs were detected in both glial-like cells and neurons. T- and H-protein mRNAs, but not P-protein mRNA, were expressed in the spinal cord. Primary astrocyte cultures established from cerebral cortex had higher GCS activities than hepatocytes whereas those from spinal cord expressed only H-protein mRNA and had no enzymatic activity. An important role of glycine as inhibitory neurotransmitter has been established in the brainstem and spinal cord and another role of glycine as an excitation modulator of N-methyl-D-aspartate receptor is suggested in the hippocampus, cerebral cortex, olfactory bulbus, and cerebellum. Our results suggest that the GCS plays a major role in the forebrain and cerebellum rather than in the spinal cord, and that N-methyl-D-aspartate receptor may participate in neuropathogenesis of NKH.

Age Factors↗
PubMed2001

T-cell receptor gammadelta T-cell leukemia with the morphology of T-cell prolymphocytic leukemia and a postthymic immunophenotype.

T-cell prolymphocytic leukemia (T-PLL) is a postthymic T-cell neoplasm with a characteristic morphology and heterogeneous immunophenotype. Most cases of T-PLL express membrane T-cell receptors (TCRs) of the alphabeta phenotype. We experienced a 30-year-old man suffering from TCRgammadelta T-cell leukemia with morphology compatible to T-PLL with a postthymic phenotype. He was admitted with skin eruption and pancytopenia. Peripheral blood and bone marrow were occupied with medium-sized lymphocytes, which had moderately condensed chromatin with a single nucleolus and sparse, nongranular basophilic cytoplasm. The immunophenotype was CD1a-, CD2-, CD3+, CD4-, CD5+, CD7+, CD8-, and terminal deoxynucleotidyl transferase negative. Hepatosplenomegaly was absent. He was diagnosed as having T-PLL and was treated with combination chemotherapy. Six months later the leukemic cell became chemoresistant. Although the patient showed transient improvement in response to pentostatin, he died 13 months after the diagnosis. To our knowledge, this is the first case of T-PLL with a TCRgammadelta phenotype.

Adult↗
PubMed2001

Therapy-related myelodysplastic syndrome/acute myeloid leukemia M2 and translocation (8;21).

An 80-year-old woman developed therapy-related myelodysplastic syndrome with translocation (8;21), which was successfully treated with an acute myeloid leukemia oriented chemotherapy. Five years before admission she had received cyclophosphamide, epirubicin, and carboplatin for endometrial cancer. The leukemia cell morphology alerted us to the possibility of the presence of t(8;21) before cytogenetic results were obtained, and AML1/ETO fusion transcript was detected by reverse transcription polymerase chain reaction. She achieved complete remission after one course of idarubicin and cytosine arabinoside. She has remained in complete remission for 6 months. Our experience suggests that recognition of typical morphological features for de novo M2 acute myeloid leukemia with t(8;21) would be important in diagnosis of therapy related myelodysplastic syndrome/acute myeloid leukemia with this translocation, which could respond to an intensive chemotherapy.

Aged↗
PubMed2001

Glu(191) and Asp(195) in rat mitochondrial processing peptidase beta subunit are involved in effective cleavage of precursor protein through interaction with the proximal arginine.

Mitochondrial processing peptidase (MPP), consisting of alpha and beta subunits, recognizes a large variety of N-terminal extension peptides of mitochondrial precursor proteins, and generally cleaves a single site of the peptide including arginine at the -2 position (P(2)). We obtained evidence that Glu(191) and Asp(195) of rat beta subunit interact with P(2) arginine of precursor protein through ionic and hydrogen bonds, respectively, using recombinant MPP. Mutation to alanines at Glu(191) and Asp(195) reduced processing activity toward precursors with P(2) arginine, but resulted in no loss of activity toward P(2) alanine precursors. Charge-complementary mutation demonstrated that MPP variants with beta Arg(191) exhibited compensatory processing activity for the precursor with acidic residue at the P(2) position. Thus, Glu(191) and Asp(195) are substrate-binding sites required for cleavage of extension peptides through interaction with P(2) arginine.

Alanine↗
PubMed2001

HLA class II-restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia-derived dendritic cells to CD4(+) T lymphocytes.

Bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones have recently been shown to augment colony formation by chronic myelogenous leukemia (CML) cells in a bcr-abl type-specific and HLA class II-restricted manner without addition of exogenous antigen. These findings suggest that CML cells can naturally process and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes in the context of HLA class II molecules. To verify this possibility, the ability of CML-derived dendritic cells (DCs) to present endogenous bcr-abl fusion protein to bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones was investigated. The bcr-abl b3a2 peptide-specific and HLA-DRB1*0901-restricted CD4+ T-lymphocyte clones produced interferon-gamma in response to stimulation with monocyte-derived DCs from HLA-DRB1*0901+ patients with b3a2 type CML. In contrast, DCs from patients with HLA-DRB1*0901- or b2a2 type CML and those from healthy individuals did not exert stimulatory activity on bcr-abl-specific CD4+ T-lymphocyte clones. The response of CD4+ T-lymphocyte clones to CML-derived mature DCs was higher than that to immature DCs and was inhibited by anti-HLA-DR monoclonal antibody. These data suggest that CML-derived DCs can process and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes.

Amino Acid Sequence↗
PubMed2001

Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences.

BACKGROUND: Mitochondrial processing peptidase (MPP) is a metalloendopeptidase that cleaves the N-terminal signal sequences of nuclear-encoded proteins targeted for transport from the cytosol to the mitochondria. Mitochondrial signal sequences vary in length and sequence, but each is cleaved at a single specific site by MPP. The cleavage sites typically contain an arginine at position -2 (in the N-terminal portion) from the scissile peptide bond in addition to other distal basic residues, and an aromatic residue at position +1. Mitochondrial import machinery recognizes amphiphilic helical conformations in signal sequences. However, it is unclear how MPP specifically recognizes diverse presequence substrates. RESULTS: The crystal structures of recombinant yeast MPP and a cleavage-deficient mutant of MPP complexed with synthetic signal peptides have been determined. MPP is a heterodimer; its alpha and beta subunits are homologous to the core II and core I proteins, respectively, of the ubiquinol-cytochrome c oxidoreductase complex. Crystal structures of two different synthetic substrate peptides cocrystallized with the mutant MPP each show the peptide bound in an extended conformation at the active site. Recognition sites for the arginine at position -2 and the +1 aromatic residue are observed. CONCLUSIONS: MPP bound two mitochondrial import presequence peptides in extended conformations in a large polar cavity. The presequence conformations differ from the amphiphilic helical conformation recognized by mitochondrial import components. Our findings suggest that the presequences adopt context-dependent conformations through mitochondrial import and processing, helical for recognition by mitochondrial import machinery and extended for cleavage by the main processing component.

Amino Acid Sequence↗
PubMed2001

Progesterone inhibits apolipoprotein-mediated cellular lipid release: a putative mechanism for the decrease of high-density lipoprotein.

In order to investigate the mechanism for female gonadal hormones to regulate the plasma high-density lipoprotein (HDL) level, the effect of 17 beta-estradiol and progestogens was examined in vitro on the assembly of HDL by free apolipoprotein A-I (apoA-I) with cellular cholesterol and phospholipid. ApoA-I generated HDL particles by removing cholesterol and phospholipid from human fibroblasts, MRC-5. While 17 beta-estradiol did not influence this reaction, progesterone suppressed the removal by apoA-I of both cholesterol and phospholipid, with the extent of the inhibition more for cholesterol than phospholipid. Three other synthetic progestogens showed the similar inhibitory effect on the cellular cholesterol release. Cellular cholesterol de novo-synthesized from mevalonolactone entered more into the acyl-esterified cholesterol compartment and less to the unesterified compartment in the presence of progesterone. On the other hand, progesterone did not influence the overall mass ratio of free and esterified cholesterol in the cell. Cell-surface cholesterol was also uninfluenced by progesterone when probed by extracellular cholesterol oxidase reaction or by diffusion-mediated cellular cholesterol release to cyclodextrin. Neither caveolin-1 nor ABCA1 expression was influenced by progesterone. Progesterone thus seems primarily to alter the specific intracellular cholesterol compartment that is related to the apoA-I-mediated HDL assembly. This mechanism might contribute to the decrease of plasma HDL by administration of progestogen in women under hormone replacement therapy.

Apolipoprotein A-I↗
PubMed2001

Cloning and expression of glucose 3-dehydrogenase from Halomonas sp. alpha-15 in Escherichia coli.

The gene encoding glucose 3-dehydrogenase (G3DH) from Halomonas sp. alpha-15 was cloned and expressed in Escherichia coli. An open reading frame of 1686 nucleotides was shown to encode G3DH. The flavine adenine dinucleotide binding motif was found in the N-terminal region of G3DH. The deduced primary structure of G3DH showed about 30% identity to sorbitol dehydrogenase from Gluconobacter oxydans and 2-keto-d-gluconate dehydrogenases from Erwinia herbicola and Pantoea citrea. The folding prediction of G3DH suggested that the 3D structure of G3DH was similar with cholesterol oxidase from Brevibacterium sterolicum or glucose oxidase from Aspergillus niger.

Amino Acid Sequence↗
PubMed2001

Li K-edge spectra of lithium halides.

We measured the Li K-edge spectra of lithium halides by means of total electron yield method (TEY), using the soft x-ray Beam Line 2 (BL2) of the compact synchrotron radiation facility at Ritsmeikan University in Japan. In lithium halides, the spectra have a sharp peak at about 60eV and a broad peak at the higher energy side. Various peak structures that appear in the absorption spectra are assigned to the corresponding Li-1s to valence band free orbitals transitions, which have been calculated by the Discrete Variational (DV)-Xalpha molecular orbital calculation method.

Journal Article↗
PubMed2001

Effects of chemotherapy on invasion and metastasis of oral cavity cancer in mice.

BACKGROUND: Using an orthotopic implantation model in which oral cancer invasion and metastasis can be reproduced, we investigated the inhibitory effects of anticancer agents on invasion and metastasis. METHODS: A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19, was implanted into the oral floor of nude mice, and cisplatin or peplomycin was administered to the mice 7 or 14 days after implantation. The effects of each anticancer drug and different administration timings on cancer invasion and metastasis were investigated. RESULTS: Tumor size and the ratio of proliferating cell nuclear antigen-positive cells was significantly reduced. In the control group, the tumors showed grade 4C mode of invasion, whereas in the groups treated with anticancer drugs, grade 3 was observed in 77.3% of the mice, with an inhibitory effect on tumor invasion being observed. The rate of metastasis in the cervical lymph node was significantly decreased in the groups treated with the cisplatin or peplomycin on day 7 after implantation. The tumor stage progression in the metastatic lymph nodes was also inhibited. CONCLUSIONS: Chemotherapy is effective not only for tumor diminution but also for inhibiting invasion and metastasis. In light of these effects, administration of anticancer drugs may be clinically useful in this regard.

Animals↗
PubMed2001

Cost-effectiveness associated with the diagnosis and staging of non-small-cell lung cancer.

OBJECTIVE: We evaluated how much time and money could be saved without compromising overall results in treating lung cancer. SUBJECTS AND METHODS: We retrospectively evaluated 318 patients for T- and M-factors and 335 for N-factor. If bronchoscopy failed to diagnose a mass lesion believed to be malignant in x-ray computed tomography (CT), we proceeded to direct thoracotomy without needle or video-assisted biopsy. When mediastinal nodes were negative in CT, we proceeded to direct thoracotomy without mediastinoscopy. We searched routinely for distant metastasis with brain and abdominal CTs and bone scans. RESULTS: Lesions suspected of malignancy in CT were pathologically malignant in 93%. A total of 82.8% of patients with CT-negative mediastinum were without metastasis. The remainder, with metastasis, had a postoperative 5-year survival of 23.5%. Brain CT scans were positive in only 2.2%, abdominal CT scans in 2.4%, and bone scans in 5.0%, for patients with a cT1/T2 non-cN2 lesion. CONCLUSION: Brain and abdominal CT scans and bone scans may be omitted for cT1/T2 and non-cN2 lesions in CT. CT-negative mediastinum then leads to direct thoracotomy. The vast majority of patients may thus undergo surgery earlier with less physical and financial burden. The cost saving was calculated to be 59.4% per cT1/T2 non-cN2 patient, or US$666,815, for population evaluated based on cost-effectiveness.

Adult↗
PubMed2001

Mediastinal neurilemmoma complicated with spinal subarachnoid hemorrhage.

A 28-year-old woman suffered severe back pain and headache during exercising on three occasions during the prior two-month period. On admission, the physical examination revealed symptoms of meningeal irritation, nuchal rigidity, severe headache, continuous nausea, and vomiting. Cerebral computed tomography of the intracranial subarachnoidal space revealed no subarachnoid hemorrhage. Her cerebrospinal fluid was bloody. Spinal magnetic resonance imaging identified a posterior mediastinal tumor adherent to the left side of the 5th thoracic vertebra and an abnormally expanded blood vessel near the mediastinal tumor. In addition, a high signal intensity lesion appeared to be present on the surface of the spinal cord. A mediastinal neoplasm was removed through standard thoracotomy. During surgery, marked enlargement was noted in some veins (hemiazygos and 5th intercostal veins) which apparently had been constricted by the mediastinal tumor. Surgical and radiological findings suggested a relationship between the constricted venous return due to the tumor and the patient's spinal subarachnoid hemorrhage.

Adult↗
PubMed2001

Concurrent Hodgkin's disease (mixed cellularity type) and T-cell chronic lymphocytic leukemia/prolymphocytic leukemia.

We describe a patient with leukopenic T-cell chronic lymphocytic leukemia/prolymphocytic leukemia (T-CLL/PLL), according to the Revised European-American Classification of Lymphoid Neoplasms. This patient simultaneously developed classic Hodgkin's disease (HD), a combination previously unreported. The leukemic cells were small and mature, did not have cytoplasmic granulation, and appeared similar to B-cell chronic lymphocytic leukemia. Immunophenotyping of the bone marrow-infiltrating cells revealed a postthymic suppressor/cytotoxic phenotype of CD2+, CD3+, CD4, CD5+, CD8+, CD25-, TCR-alpha beta. A lymph node biopsy showed the histological features of HD (mixed cellularity) with infiltrating CD8+ lymphocytes, and immunohistochemical examination revealed the following phenotype of Reed-Sternberg cells: LeuM1/CD15+, BerH2/CD30+, L26/PanB-, UCHL-1/CD45RO-, cyCD3-, CD4, CD8-, CD20-, CD79a-, EMA-, EBER-1+, LMP-1+. Southern blot analysis of the bone marrow and lymph node revealed the same rearrangement of bands of T-cell-receptor genes. Although the HD was treated with chemotherapy that resulted in complete remission, the T-PLL/CLL took an indolent course. This case may suggest the existence of a subtype of T-CLL/PLL with leukopenia and an indolent clinical course. Both diseases were believed to be independent and not a transformation of one to the other.

Aged↗
PubMed2001

MR imaging of clear cell carcinoma of the ovary.

Magnetic resonance imaging findings are reported for 12 pathologically proven lesions of clear cell carcinoma (CCC) of the ovary in 11 women (mean age 50 years). T1- and T2-weighted MR images were obtained in all patients, and gadolinium-enhanced MR images were obtained in 9. The mean diameter of the tumors was 13 cm. Seven patients presented with stage-I tumors. All 12 lesions consisted of cystic masses with solid protrusions occurring in 10 and solid masses in 2. The cysts were unilocular in 9 lesions and multilocular in 1. In four lesions, the cysts displayed with high intensity on T1-weighted images. Round solid protrusions were identified in 8 lesions. In 5 lesions, the number of protrusions was only a few. The solid portions of 5 masses had slightly high-intensity regions on T1-weighted images. The number of patients with ascites was three. Magnetic resonance imaging of CCC usually shows a unilocular large cyst with solid protrusions, which are often round and few in number. Such MR imaging findings suggest malignant tumor but are not specific.

Adenocarcinoma, Clear Cell↗
PubMed2001

Double cancers in the common bile duct: molecular genetic findings with an analysis of LOH.

We report a 69-year-old man with double cancers in the common bile duct. One cancer was located between the superior and middle parts of the bile duct, while the other cancer was in the inferior part of the bile duct. Pylorus-preserving pancreatoduodenectomy was performed. There was no communication between the two cancers in either the mucosal layer or the subepithelial layer. On pathological examination, the upper cancer was diagnosed as poorly differentiated adenocarcinoma, while the lower one was found to be moderately differentiated adenocarcinoma. We analyzed loss of heterozygosity (LOH), using microsatellite markers on five chromosomal arms, in both the upper and the lower cancers. Both cancers showed common regions of LOH at 5q, 6q, 9p, 17p, and 18q, whereas the upper cancer showed one additional region of LOH at 8p, thus suggesting progression, due to the acquisition of the additional LOH, in the upper cancer. No LOH was observed in the region between the two cancers. The presence of one additional LOH in the upper cancer suggests that the upper cancer was a metastasis of the lower one.

Adenocarcinoma↗